NON-NATURAL AMINO ACIDS IN PEPTIDE DRUG DEVELOPMENT

肽药物开发中的非天然氨基酸

• 批准号: 6585217
• 负责人: THOMAS A DIX
• 金额: $ 12.53万
• 依托单位: ARGOLYN BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6585217
• 关键词: aminoacid; biotherapeutic agent; blood brain barrier; drug design /synthesis /production; drug metabolism; laboratory rat; pain; peptide chemical synthesis; peptides; pharmacokinetics

DESCRIPTION (provided by applicant): Argolyn Bioscience Inc. is an early stage biotechnology company that creates novel peptide drugs and diagnostics with greatly improved intrinsic pharmaceutical properties through substitution of non-natural amino acid analogues for arginine (Arg) or lysine (Lys). In proof-of concept studies thus far, application of the Argolyn technology to peptides of therapeutic interest has resulted in dramatic increases in receptor binding, induction of receptor selectivity, blood and plasma stabilization, and delivery through the blood brain barrier (BBB). A key question for our technology is its breadth: can any peptide of biological interest be improved? The Company currently has late-discovery-stage lead candidates in psychosis, pain, and thrombosis; the psychosis and thrombosis leads are being pursued through other STTRs (submitted) and currently active grants. In this proposal, we will use ABS17, our lead candidate in pain, as another vehicle with which to evaluate the robustness of the technology. We propose to evaluate the systemic pharmacokinetics, blood brain barrier access, oral bioavailability, microsomal stability, and preliminary toxicity of ABS17. Completion of the Specific Aims of this proposal, in combination with data already accumulated on this peptide, will "round out" the preclinical work and provide a third peptide candidate on which the Argolyn platform was successfully applied. It will also lead directly into the Phase 2 STTR that will address the technology more generically (immunogenicity, toxicity of the individual non-natural amino acid residues, and model peptides containing them, etc.).

描述（由申请人提供）：Argolyn Bioscience Inc.是一家早期的生物技术公司，通过替代非天然氨基酸类似物（ARG）或赖氨酸（lys）（lys），创建具有大大改善内在药物特性的新型肽药物和诊断。在迄今为止的概念证明研究中，将Argolyn技术应用于治疗兴趣的肽，导致受体结合，受体选择性，血液和血浆稳定性的诱导以及通过血脑屏障（BBB）的递送的急剧增加。我们技术的关键问题是它的广度：可以改善生物学兴趣的任何肽吗？该公司目前在精神病，疼痛和血栓形成方面有晚期发现的主要候选人；精神病和血栓形成铅正在通过其他STTR（已提交）和目前积极的赠款来追求。在此提案中，我们将使用ABS17（痛苦中的主要候选人）作为另一种评估技术鲁棒性的工具。我们建议评估全身药代动力学，血脑屏障的进入，口服生物利用度，微粒体稳定性以及ABS17的初步毒性。该提案的具体目的的完成，结合已经在该肽上累积的数据结合，将“舍入”临床前工作，并提供第三个成功应用Argolyn平台的候选候选者。它还将直接进入2阶段的STTR，该阶段将更加普遍地解决该技术（免疫原性，单个非天然氨基酸残基的毒性以及含有它们的肽的模型等）。